| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| Other Sizes |
| Targets |
IDH-305 targets mutant isocitrate dehydrogenase 1 (IDH1), specifically the R132 mutant forms. Mutant IDH1 produces the oncometabolite 2-hydroxyglutarate (2-HG), which promotes tumorigenesis. By selectively inhibiting mutant IDH1, IDH-305 reduces the production of 2-HG, thereby disrupting tumor metabolism and exerting antitumor effects. It has IC50s of 27 nM for IDH1R132H and 28 nM for IDH1R132C.
|
|---|---|
| ln Vitro |
HCT116-IDH1R132H+/- cells are inhibited by IDH-305 with an IC50 of 24 nM[1].
IDH-305 is a potent and selective inhibitor of mutant IDH1, with IC50s of 27 nM for IDH1R132H, 28 nM for IDH1R132C, and 6.14 μM for wild-type IDH1. It exhibits greater than 200-fold selectivity for mutant IDH1 isoforms over the wild-type enzyme. Its activity has been confirmed in various in vitro assays using recombinant enzymes and cell lines expressing mutant IDH1. |
| ln Vivo |
In the IDH1 mutant PDX melanoma model, IDH-305 (30-300 mg/kg; route; twice daily for 21 days) suppresses 2-HG production and 2-HG increases tumor growth [1].
IDH-305 is an orally available and brain-penetrant inhibitor. It has been shown to reduce 2-HG production in preclinical models. Its ability to penetrate the brain makes it potentially useful for the treatment of gliomas and other brain tumors with IDH1 mutations. However, detailed in vivo efficacy data in animal models is limited. |
| Enzyme Assay |
The primary in vitro assay for IDH-305 is an enzyme activity assay using purified recombinant wild-type or mutant IDH1. The enzyme is incubated with its substrate, isocitrate, and the production of 2-HG is measured in the presence of the compound. The IC50 values are determined from dose-response curves. The selectivity for mutant over wild-type IDH1 is assessed in parallel assays.
|
| Cell Assay |
In vitro cellular experiments for IDH-305 involve treating cancer cell lines expressing mutant IDH1 with the compound and measuring its effects on 2-HG production and cell proliferation. 2-HG levels are measured by mass spectrometry. Cell proliferation and viability are assessed using standard assays such as MTT or CellTiter-Glo. The effects on downstream signaling pathways and gene expression are also assessed.
|
| Animal Protocol |
Animal/Disease Models: nu /nu (nude) mice (HMEX2838-IDH1R132C+/-PDX model) [1]
Doses: 30, 100, 300 mg/kg Route of Administration: po (oral gavage); twice a day for 21 days Experimental Results: 100 mg/ kg, 2-HG was diminished by 62-67%, showing significant anti-tumor activity; at 300 mg/kg, 2-HG was diminished by 97-99%, and some tumors were diminished by 32%. In vivo animal experiments for IDH-305 have been conducted in xenograft models of cancers harboring IDH1 mutations. The compound is administered orally, and its effects on tumor 2-HG levels, tumor growth, and survival are assessed. Its pharmacokinetic properties, including brain penetration, are also characterized. |
| ADME/Pharmacokinetics |
IDH-305 has a molecular weight of 511.43 g/mol and a molecular formula of C23H20F4N6O2. It is an orally available and brain-penetrant small molecule. It is soluble in DMSO. It is typically used as a research reagent and is stored as a powder at -20°C for long-term stability. Its purity is typically ≥98%.
|
| Toxicity/Toxicokinetics |
IDH-305 is a research compound that is not intended for human use. Its toxicological profile is not extensively characterized in the available literature. As with all research chemicals, standard safety precautions should be followed when handling. Its safety would need to be established for therapeutic applications.
|
| References |
|
| Additional Infomation |
IDH-305 is an orally available, mutant-selective, and brain-penetrant inhibitor of IDH1 that targets the R132 mutation. It has IC50s of 27 nM for IDH1R132H and 28 nM for IDH1R132C, with >200-fold selectivity over wild-type IDH1. IDH-305 reduces the production of the oncometabolite 2-HG and is being developed for the treatment of IDH1-mutant cancers.
|
| Molecular Formula |
C23H22F4N6O2
|
|---|---|
| Molecular Weight |
490.453398227692
|
| Exact Mass |
490.174
|
| CAS # |
1628805-46-8
|
| PubChem CID |
90415637
|
| Appearance |
White to off-white solid powder
|
| LogP |
3.9
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
11
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
35
|
| Complexity |
731
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
F[C@@H](C)[C@H]1COC(N1C1C=CN=C(N[C@@H](C)C2C=C(C)C(C3C=CN=C(C(F)(F)F)C=3)=CN=2)N=1)=O
|
| InChi Key |
DCGDPJCUIKLTDU-SUNYJGFJSA-N
|
| InChi Code |
InChI=1S/C23H22F4N6O2/c1-12-8-17(30-10-16(12)15-4-6-28-19(9-15)23(25,26)27)14(3)31-21-29-7-5-20(32-21)33-18(13(2)24)11-35-22(33)34/h4-10,13-14,18H,11H2,1-3H3,(H,29,31,32)/t13-,14-,18+/m0/s1
|
| Chemical Name |
(R)-4-((S)-1-fluoroethyl)-3-(2-(((S)-1-(4-methyl-2'-(trifluoromethyl)-[3,4'-bipyridin]-6-yl)ethyl)amino)pyrimidin-4-yl)oxazolidin-2-one
|
| Synonyms |
IDH305; IDH-305; IDH 305
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ≥ 150 mg/mL (~305.8 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.10 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.10 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0389 mL | 10.1947 mL | 20.3894 mL | |
| 5 mM | 0.4078 mL | 2.0389 mL | 4.0779 mL | |
| 10 mM | 0.2039 mL | 1.0195 mL | 2.0389 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
